You’ll want to use different fonts for the paper and any ebook/Web versions of your book. That’s because the eye responds differently to varying platforms for reading. A billboard likely will use large blocky letters while a magazine can get away with using typefaces in which the letters are thin.
Regarding books, for the paper version use a serif font. Some studies indicate that serif typefaces are easier to read in print. I’d recommend Garamond, Calibri or Georgia. Stay away from Times New Roman, though, as it is a bit overused.
For an ebook or any website, use a sans-serif typeface. I’d suggest Arial, Trebuchet MS or Cambria. Avoid Helvetica, as it tends to be overused. Note that with ebooks, many self-publishing companies have pre-selected a single typeface, so you may have no choice in the matter.
Further, what’s easy on the eyes today may not be so easy tomorrow. Typefaces are children of trends, though this change occurs much more slowly than do the color of the year in fashion or the style of popular music. If this book is still in print 20 years from now, though, I’m confident today that I’ll need to change the above typeface recommendations to meet what will be popular then.
For the most part, your text will appear in the regular font of the typeface you select. Sometimes to emphasize a word, though, you will opt to place it in an italicized font of that typeface. That’s cool.
Sometimes it’s underscored instead, though. That’s not so cool, as it raises the question of which approach you prefer: underscore or italics? Then sometimes the word is both italicized and underlined. That’s definitely not cool at all. You’ll want to select one style and stick to it.
Whether to use italics or underscores is largely a matter of your publisher’s preference. In the absence of that, I’d recommend italics, as that’s ultimately what an underlined word tells a typesetter to do – to italicize the word – and in the age of word processing, we rarely use typesetters anymore.